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Understanding the biology of intrinsic aging is important for geriatricians because of the insights it provides into: (i) why and how the body becomes progressively more vulnerable to disability and disease as we grow older; (ii) how we might intervene in the underlying mechanisms; and (iii) what is the exact nature of the relationship between “normal” aging and age-related diseases. Although there is significant variability in how aging affects individuals, certain underlying processes appear to follow a common course. Furthermore, humans share some features of aging with a wide range of other animal species. Thus, even though much of the research on intrinsic aging is done using simple animal models such as the roundworm Caenorhabditis elegans or the fruitfly Drosophila melanogaster, it appears that common regulatory pathways are at least partially conserved across the spectrum that includes mammals, and in particular humans. This is especially the case for fundamental mechanisms that protect cells against shared threats such as damage to DNA arising from endogenous stressors like reactive oxygen species (ROS), which are essential molecular by-products of the body's dependence on oxygen to provide energy.

Why Aging Occurs

One of the central questions in the biology of aging is the nature of the genetic contribution to longevity. How do genes act on the aging process, and how does an individual's genetic endowment contribute to their longevity?

Aging and longevity are clearly influenced by genes. Firstly, the life spans of human monozygotic twin pairs are more similar than life spans of dizygotic twins. Secondly, there are differences in life span between different genetically inbred strains of any given laboratory animal, such as the mouse. Thirdly, studies of simple organisms like fruit flies, nematode worms, and yeast have identified gene mutations that affect duration of life. However, although genes influence longevity, genes appear to account for only about 25% of the variance in human life span.

The nature of the genetic contribution to the aging process has received much attention, both from the perspective of evolutionary theory and through experimentation. The evolutionary angle is valuable because it can tell us a great deal about the kinds of genes that are likely to underlie the aging process. A commonly held belief is that aging evolved as an evolutionary necessity—for instance, to remove older individuals who might otherwise consume resources needed by the young. However, there is little support for the idea that aging does actually fulfill such a role. In nature, the vast majority of animals die young, long before they could become obstructive to the interests of the next generation. Out of a population of newborn wild mice, for example, nine out of 10 of them will be dead before 10 months even though half of the same animals reared in captivity would still be alive at 2 years. Thus, aging in mice is seen only in protected environments, and until relatively recently the same ...

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